Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol is metabolized in the brain by catalase/H2O2 to yield acetaldehyde and by an ethanol-inducible form of cytochrome P450 (P450 IIE1) in a reaction that yields oxygen radicals. Within the cytoplasm of serotonergic axon terminals these metabolic pathways together provide conditions for the endogenous synthesis of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), by reaction of acetaldehyde with unbound 5-hydroxytryptamine (5-HT), and for the oxygen radical-mediated oxidation of this alkaloid. The major initial product of the hydroxyl radical (HO.)-mediated oxidation of 1 in the presence of free glutathione (GSH), a constituent of nerve terminals and axons, is 8-S-glutathionyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (6). When administered into the brains of mice, 6 is a potent toxin (LD50 = 2.9 microg) and evokes episodes of hyperactivity and tremor. Compound 6 binds at the GABA(B) receptor and evokes elevated release and turnover of several neurotransmitters. Furthermore, the GABA(B) receptor antagonist phaclofen attenuates the behavioral response caused by intracerebral administration of 6. These observations suggest that 6 might be an inverse agonist at the GABA(B) receptor site. Accordingly, it is speculated that ethanol drinking might potentiate formation of 6 that contributes to elevated release of several neurotransmitters including dopamine (DA) and endogenous opioids in regions of the brain innervated by serotonergic axon terminals. Subsequent interactions of DA and opioids with their receptors might be related to the initial development of dependence on ethanol. Redox cycling of 6 (and of several putative secondary metabolites) in the presence of intraneuronal antioxidants and molecular oxygen to produce elevated fluxes of cytotoxic reduced oxygen species might contribute to the degeneration of serotonergic pathways. Low levels of 5-HT in certain brain regions of the rat predisposes these animals to drink or augments drinking. Accordingly, 6, formed as a result of ethanol metabolism in the cytoplasm of certain serotonergic axon terminals, might contribute to the initial development of dependence on ethanol, by mediating DA and opioid release, and long-term preference and addiction to the fluid as a result of the progressive degeneration of these neurons.
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PMID:Putative oxidative metabolites of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline of potential relevance to the addictive and neurodegenerative consequences of ethanol abuse. 916 Jul 98

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.
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PMID:Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. 926 9

We modified the isolation procedure of muscle and heart mitochondria. In human muscle, this resulted in a 3.4 fold higher yield of better coupled mitochondria in half the isolation time. In a preparation from rat muscle we studied factors that affected the stability of oxidative phosphorylation (oxphos) and found that it decreased by shaking the preparation on a Vortex machine, by exposure to light and by an increase in storage temperature. The decay was found to be different for each substrate tested. The oxidation of ascorbate was most stable and less sensitive to the treatments. When mitochondria were stored in the dark and the cold, the decrease in oxidative phosphorylation followed first order kinetics. In individual preparations of muscle and heart mitochondria, protection of oxidative phosphorylation was found by adding candidate stabilizers, such as desferrioxamine, lazaroids, taurine, carnitine, phosphocreatine, N-acetylcysteine. Trolox-C and ruthenium red, implying a role for reactive oxygen species and calcium-ions in the in vitro damage at low temperature to oxidative phosphorylation. In heart mitochondria oxphos with pyruvate and palmitoylcarnitine was most labile followed by glutamate, succinate and ascorbate. We studied the effect of taurine, hypotaurine, carnitine, and desferrioxamine on the decay of oxphos with these substrates. 1 mM taurine (n = 6) caused a significant protection of oxphos with pyruvate, glutamate and palmitoylcarnitine, but not with the other substrates. 5 mM L-carnitine (n = 6), 1 mM hypotaurine (n = 3) and 0.1 mM desferrioxamine (n = 3) did not protect oxphos with any of the substrates at a significant level. These experiments were undertaken in the hope that the in vitro stabilizers can be used in future treatment of patients with defects in oxidative phosphorylation.
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PMID:Rapid isolation of muscle and heart mitochondria, the lability of oxidative phosphorylation and attempts to stabilize the process in vitro by taurine, carnitine and other compounds. 930 66

Surface topography plays an important role in cell orientation and morphogenesis. In this study, we prepared a micropatterned surface with settling particles to obtain more detailed information about the cell recognition against the microstructured surface. Core-shell type particles having a poly-(N-isopropylacrylamide) (polyNIPAM) shell were prepared by seeded polymerization. Particles were settled on a polystyrene (PSt) flat dish by the spinner to prepare a micropatterned surface with settling particles. It could be seen that the polyNIPAM shell shrunk above and swelled below the LCST. For comparison, a thermosensitive flat surface was prepared by the graft polymerization of NIPAM. No morphologic change of cells contacting the both surfaces was observed with either an optical or a scanning electron microscope. Moreover, particles could move or roll on these surfaces when shaking the dishes. The weak interaction between neutrophil-like cells and the micropatterned surface with settling particles or the polyNIPAM-grafted surface was estimated by measurement of active oxygen released by cells. A little release could be observed at both 25 and 35 degrees C. The amount of released active oxygen at 35 degrees C was slightly larger than at 25 degrees C. When the temperature was suddenly changed, the dynamic changes of particle shape and size resulted in the excess release of active oxygen from cells contacting the micropatterned surface with settling particles. Meanwhile no stimulation could be observed in the polyNIPAM-grafted surface even if the temperature is suddenly changed. These results indicate that the micropatterned surface with settling particles can induce the dynamic stimulus at a patterned input mode.
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PMID:Cell activation by the micropatterned surface with settling particles. 934 53

Positron emission tomography (PET) scanning provides a sensitive means of detecting and characterizing regional changes in brain metabolism and receptor binding in movement disorders. PET allows the quantitative examination of regional cerebral blood flow, regional glucose and oxygen metabolism, and brain pharmacology. In this article, the particular use of PET to determine the effects of therapeutic stereotactic surgery, including transplantation, on brain function in Parkinson's disease and in tremor patients is highlighted.
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PMID:Positron emission tomography studies in movement disorders. 949 90

Simple cold storage of livers for transplantation activates glycolysis due to lack of oxygen. Energy derived from glycolysis may be critical for cell survival and liver cell death may occur once glycolysis is inhibited in the liver due to accumulation of end products or lack of substrates (glycogen). The relationship between cell death (lactate dehydrogenase, LDH release), anaerobic glycolysis (lactate production), and glycogen content of liver tissue was studied during cold incubation of liver slices in UW solution. Rat livers slices from male Sprague Dawley rats were incubated at 4 degrees C in UW solution, with continuous gentle shaking, under conditions of chemical hypoxia (KCN, 5 mM). The rate of lactate production, LDH release-ATP and glycogen content were measured spectrophotometrically and by HPLC. Lactate increased nearly linearly for the first 48 h of incubation; total lactate which had accumulated after 48 h was 33.9 +/- 0.81 mumol/g and at 96 h nearly the same, 31.3 +/- 1.2 mumol/g. Glycolysis stopped, apparently, because of the depletion of liver slice glycogen which was initially 228.8 +/- 1.7 mumol/g wet wt. It decreased to 34.7 +/- 2.7 mumol/g at 48 h and to 18.7 +/- 1.1 mumol/g at 72 h and remained at this level for the next 24 h. An increased leakage of LDH occurred once glycogen metabolism (and accumulation) ceased. LDH release could be stimulated after only a few hours of cold incubation of liver tissue slices by adding glycolysis inhibitor (iodoacetic acid) to the medium. After 24 h. LDH release was 24.4 +/- 1.8% and increased to 52.8 +/- 5.2% (P < 0.05, Student's t-text) with iodoacetic acid. Adding a glycolytic substrate (fructose, 10 mM) to the medium maintained lactate production for 96 h. The stimulation of glycolysis by fructose also reduced cell death: LDH release was significantly lower at 72- and 96-h incubation (P < 0.001, two-way ANOVA). The ATP content was significantly higher with fructose (P < 0.001). Adding glucose (20 mM) and fructose (10 mM) in combination resulted in prolonged cell survival, significantly delayed glycogen depletion and significantly higher ATP content at 48 and 72 h (two-way ANOVA). Livers from rats who had fasted for 24 h demonstrated the same LDH release at 48 h when incubated with glucose (20 mM) and fructose (10 mM). In conclusion, LDH leakage from hypoxic cold-stored liver slices is related to anaerobic glycolysis. Anaerobic glycolysis appears to continue slowly under hypothermia and provides sufficient energy for maintenance of cell viability. A stimulation of glycolysis in the cold is possible by fructose and results in prolonged cell survival under hypothermic conditions. Glycogen depletion can be slowed down by combining glucose and fructose.
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PMID:[Liver metabolism during cold ischemic incubation in UW solution in the rat model]. 949 7

Infants subjected to repeated episodes of violent shaking develop brain damage characterized by intracranial hemorrhage and progressive cortical atrophy. We have developed an animal model that mimics this pathological state and investigated its etiology and treatment. Anesthetized male rats, 6 days of age, were subjected to one episode of shaking per day for 3 consecutive days. Separate groups of rats were sacrificed 1 h postinjury on the third day of shaking for HPLC quantification of cortical .OH and vitamin E levels, and histological assessment of cortical hemorrhaging. Additional groups were sacrificed 7 or 14 days postinjury to demonstrate progressive neuronal degeneration via cortical wet weight comparisons. In comparison to noninjured shams, the results indicated that cortical vitamin E and .OH levels rose 53.7% (p < 0.005) and 457.1% (p < 0.001), respectively, in shaken infant rats. Brain histologies revealed a moderate-to-severe degree of cortical hemorrhaging in these animals 1 h postinjury. By 7 and 14 days postinjury, there was a 13.3% and 28.7% (p < 0.0001 vs. sham) loss of cortical tissue in shaken infants, respectively, indicating progressive neuronal degeneration. Treatment with 10 mg/kg (ip) of the 21-aminosteroid antioxidant, tirilazad mesylate, 10 min before and 2 h after each episode of shaking, resulted in a 53.1% attenuation of cortical .OH levels and a 34.9% decrease in brain hemorrhaging (p < 0.05 vs. vehicle). Tirilazad treatment did not, however, significantly effect cortical vitamin E concentrations at 1 h postinjury or the extent of progressive neuronal degeneration at either 7 or 14 days postinjury. The present animal model mimics the brain pathology seen in abused children. Our observation that tirilazad mesylate, an antioxidant-lipid peroxidation inhibitor, significantly reduces cortical .OH levels and brain hemorrhaging in shaken infant rats supports a role for oxygen radicals in the pathophysiology of this type of CNS injury. The failure of tirilazad to block progressive cortical degeneration suggests that mechanisms other than free radicals may be of prime importance in the mediation of this aspect of the pathology.
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PMID:Infant rat model of the shaken baby syndrome: preliminary characterization and evidence for the role of free radicals in cortical hemorrhaging and progressive neuronal degeneration. 975 17

We studied how male fifteen-spined sticklebacks, Spinachia spinachia, vary in paternal competence, whether males advertise their competence and whether females prefer better fathers. In this species the male alone provides care for the offspring through nest building, fanning, cleaning and protecting the eggs. We found no female preference for larger males. Instead, females preferred males that during the subsequent paternal phase fanned their nests in shorter fanning bouts. Such males enjoyed a significantly higher hatching success because they fanned more often than males with longer fanning bouts. Males that fanned for short bouts during the paternal phase were also able to increase their fin beat rate. Frequent fanning and high fin beat rates may improve the flow of oxygen to the eggs. Beat rate may be a condition-dependent trait, because males that lost more weight were unable to increase their fin beat rate. During courtship, males perform behaviours such as displacement fanning and body shaking. Females preferred males showing more frequent body shakes during courtship. Body shake frequency correlated positively with hatching success, and negatively with mean fanning bout duration during the paternal phase. The results indicate that female S. spinachia show a preference for direct benefits in terms of better paternal care, and that males may signal this ability to females by shaking their body during courtship. Copyright 1998 The Association for the Study of Animal Behaviour.
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PMID:Female fifteen-spined sticklebacks prefer better fathers. 981 34

Manual vibratory massage is part of the preventive physiotherapeutic activities performed in intensive care units. The vibratory massage can be performed manually or as electrovibratory massage. The manual massage is a fast rhythmical vibration performed by the arm and shoulder muscles of the masseur and transferred to the patient's thorax by the hand. The hand of the masseur has to achieve a tremor with a frequency of 8 to 11 tremors/s. The aim of the pilot study was to examine the influence of manual vibratory massage on the pulmonary function of postoperative patients who were receiving mechanical ventilation, with special interest being focused on pulmonary ventilation and perfusion and cerebral blood flow velocity. Manual vibratory massage was performed postoperatively in the intensive care unit on eight patients: three patients had undergone heart transplantation, three had undergone lung transplantation, and two had undergone coronary artery bypass grafting (mean age, 53.6+/-8 yr). With the aid of continuous monitoring, we examined the changes of the respiration parameters and the cerebral blood flow velocity (measured by transcranial Doppler sonography). The vibratory massage was performed with a frequency of 8 to 10 vibrations/s for 15 min, 7.5 min on each side of the thorax, starting from the lower costal arch and progressing to the upper thoracic aperture. For 10 min before, during, and 10 min after the massage, the parameters of peripheral oxygen saturation, central venous pressure, mean arterial pressure, heart rate, lung resistance and compliance, tidal volume, respiration rate, and cerebral blood flow velocity were recorded at 2-min intervals. Moreover, before and after vibratory massage, arterial blood gases were determined. In four of the eight patients, it was possible to determine pulmonary arterial pressure, pulmonary capillary wedge pressure, as well as pulmonary vascular resistance. During the vibratory massage, we could prove a significant increase of the mean tidal volume by 30% (P = 0.008). The percutaneous oxygen saturation significantly increased also, from 92 to 93.6% (P = 0.002). Central venous pressure significantly decreased by 11% (P = 0.04), and pulmonary vessel resistance was reduced by 18.3% (P = 0.001). The pulmonary resistance decreased from 10.5 to 9.2 H2O/l/s (P < 0.05) by the end of the observation period. Cerebral blood flow velocity showed no significant change. Vibratory massage seems to improve pulmonary mechanism and perfusion, thus, reducing ventilation perfusion mismatch and increasing oxygen saturation.
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PMID:External stimuli in the form of vibratory massage after heart or lung transplantation. 1008 83

beta 2 agonists are first election drugs for the treatment of asthma exacerbations. However, rates of complications derived from this asthma therapy like cardiovascular effects have addressed question marks on a possible paradoxical condition, leading to an increased mortality rate. The study was open label, non controlled and aimed to assess the effect of albuterol nebulizations on serum potassium levels, arterial oxygen saturation and electrocardiographic changes in asthma exacerbation in pediatric patients. Albuterol was administered at a dose of 150 mcg/kg/course for 10 minutes in two occasions. Thirty children with mild to moderate asthmatic exacerbation, admitted to emergency room, were included in the study. Bronchodilators administration in the previous 24 hours and history of cardiac or metabolic disease were considered exclusion criteria. Drugs affecting serum potassium were not allowed. Severity of exacerbation was rated by the Wood-Downes criteria. Average sample age was 7.4 +/- 1 years, heart rate increased from 111 +/- 23.23 to 130.0 +/- 22.14 beats/minute, with no clinical significance; serum potassium levels decreased from 4.47 +/- 0.52 to 3.73 +/- 0.49 mEq/L between baseline and final visits, respectively; QTc interval was significantly enlarged from 0.397 to 0.418 milliseconds between initial and final records (p < 0.001), but had no clinical meaning. No arrhythmias were recorded. Pulse oxymetry did not show significant changes (90.6 +/- 3.0% and 92.1 +/- 3.2 at baseline and final visits). The most common reported adverse event was distal tremor, which was present in 80% of the cases. Neither serum potassium decrement nor prolonged QTc after albuterol had clinical significance. Albuterol is a safe drug for the treatment of mild to moderate asthma exacerbations in pediatric patients.
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PMID:Metabolic and electrocardiographic effects of albuterol in pediatric asthmatic patients treated in an emergency room setting. 1021 68


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